Organic anion transporting peptide-based cancer imaging and therapy

Abstract

A dye-drug conjugate for preventing, treating, or imaging cancer having the following structure:wherein R1 and R2 are independently selected from the group consisting of —H, alkyl, alkyl-sulphonate, alkylcarboxylic, alkylamino, aryl, —SO3H, —PO3H, —OH, —NH2, and -halogen; wherein Y1 and Y2 is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylsulphonate, alkylcarboxylic, alkylamino, ω-alkylaminium, ω-alkynyl, PEGyl, PEGylcarboxylate, ω-PEGylaminium, ω-acyl-NH, ω-acyl-lysinyl-, ω-acyl-triazole, ω-PEGylcarboxyl-NH—, ω-PEGylcarboxyl-lysinyl, and ω-PEGylcarboxyl-triazole; wherein X is selected from the group consisting of a hydrogen, halogen, CN, Me, NH2, SH and OH; and R3 and R4 are independently a hydrogen, a therapeutic agent, or an imaging moiety, wherein the therapeutic agent is selected from the group consisting of a platinum-based therapeutic agent, a small molecule therapeutic agent, a peptide, a protein, a polymer, an siRNA, a microRNA, and a nanoparticle, wherein the imaging is a radio-isotope selected from the group consisting of F18, I-125, I-124 I-123, I-131, and small molecule labeled with any of these isotopes, or wherein the imaging moiety is a chelator-complexed radioactive isotope, wherein the radioactive isotope is selected from the group consisting of Cu-64, In-111, Tc-99m, Ga-68, Lu-177, Zo-89, Th-227 and Gd-157.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a national stage application of, and claims the benefit to, PCT Application No. PCT / US2015 / 067393 filed Dec. 22, 2015, which claims priority to U.S. Patent Application Ser. No. 62 / 095,713, filed Dec. 22, 2014, the entire disclosures of which are incorporated herein by reference.TECHNICAL FIELD OF THE INVENTION[0002]A dye-drug conjugate for preventing, treating, or imaging cancer having the following structure:[0003]wherein R1 and R2 are independently selected from the group consisting of —H, alkyl, alkyl-sulphonate, alkylcarboxylic, alkylamino, aryl, —SO3H, —PO3H, —OH, —NH2, and -halogen; wherein Y1 and Y2 is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylsulphonate, alkylcarboxylic, alkylamino, ω-alkylaminium, ω-alkynyl, PEGyl, PEGylcarboxylate, ω-PEGylaminium, ω-acyl-NH, ω-acyl-lysinyl-, ω-acyl-triazole, ω-PEGylcarboxyl-NH—, ω-PEGylcarboxyl-lysinyl, and ω-PEGylcarboxyl-triazole;...

AI Technical Summary

Benefits of technology

The present invention is based on the use of NIR dye-drug conjugates to treat and diagnose cancer in humans. These conjugates have the ability to be taken up and retained by cancer cells, but not by normal cells, using OATPs. The chemical entities of the NIR dye-drug conjugates include a targeting ligand, therapeutic agents, and a linker connecting the targeting ligand to the therapeutic agents. The invention has been found to be effective in treating and diagnosing cancer in mice and may offer a more effective, targeted therapy for human prostate, pancreatic, and brain tumors, which currently have no effective therapy.

Problems solved by technology

Third, the inventor demonstrated the effectiveness of these NIR dye-drug conjugates in the most deadly human tumors known to cause significant mortality and morbidity in men and currently there is no effectiveness therapy, namely, human prostate and pancreatic cancers, and brain tumors.

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